TRPV4 mediates the Ca2+ influx required for the interaction between flightless-1 and non-muscle myosin, and collagen remodeling - PubMed (original) (raw)
. 2017 Jul 1;130(13):2196-2208.
doi: 10.1242/jcs.201665. Epub 2017 May 19.
Affiliations
- PMID: 28526784
- DOI: 10.1242/jcs.201665
TRPV4 mediates the Ca2+ influx required for the interaction between flightless-1 and non-muscle myosin, and collagen remodeling
Pamma D Arora et al. J Cell Sci. 2017.
Abstract
Fibroblasts remodel extracellular matrix collagen, in part, through phagocytosis. This process requires formation of cell extensions, which in turn involves interaction of the actin-binding protein flightless-1 (FliI) with non-muscle myosin IIA (NMMIIA; heavy chain encoded by MYH9) at cell-matrix adhesion sites. As Ca2+ plays a central role in controlling actomyosin-dependent functions, we examined how Ca2+ controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca2+ influx at the extensions of fibroblasts. Western blotting and quantitative (q)PCR showed high expression levels of the Ca2+-permeable transient receptor potential vanilloid-4 (TRPV4) channel, which co-immunoprecipitated with β1 integrin and localized to adhesions. Treatment with α2β1-integrin-blocking antibody or the TRPV4-specific antagonist AB159908, as well as reduction of TRPV4 expression through means of siRNA, blocked Ca2+ influx. These treatments also inhibited the interaction of FliI with NMMIIA, reduced the number and length of cell extensions, and blocked collagen remodeling. Pulldown assays showed that Ca2+ depletion inhibited the interaction of purified FliI with NMMIIA filaments. Fluorescence resonance energy transfer experiments showed that FliI-NMMIIA interactions require Ca2+ influx. We conclude that Ca2+ influx through the TRPV4 channel regulates FliI-NMMIIA interaction, which in turn enables generation of the cell extensions essential for collagen remodeling.
Keywords: Actin; Ca2+; Cell extensions; Extracellular matrix; Remodeling.
© 2017. Published by The Company of Biologists Ltd.
Conflict of interest statement
Competing interestsThe authors declare no competing or financial interests.
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